Management of Hemorrhage in Trauma
Herbert Schöchl, MD,*† Alberto Grassetto, MD,‡ and Christoph J. Schlimp, MD†
Hemorrhage remains one of the leading causes of trauma-
related deaths. Uncontrolled diffuse microvascular bleeding
in the course of initial care is common, potentially resulting
in exsanguination. Early and aggressive hemostatic inter-
vention increases survival and reduces the incidence of
massive transfusion. Thus, timely diagnosis of the under-
lying coagulation disorders is mandatory. It has been shown
that standard coagulation tests do not sufficiently character-
ize trauma-induced coagulopathy (TIC). This has led to
increasing interest in alternatives, such as the viscoelastic
test, to diagnose TIC and to provide the basis for a goal-
directed hemostatic therapy.
The concept of damage control resuscitation (DCR) has been
introduced widely in trauma patients with severe bleeding.
I N-HOSPITAL EXSANGUINATION has been reported in
26% to 39% of all casualties in civilian trauma centers.1,2
Furthermore, it is assumed that up to 20% of trauma-associated
deaths potentially are preventable if early and rapid control of blood
loss and coagulopathy could be established.3 The majority of these
patients exsanguinate due to injuries of the thorax, abdomen, and
pelvis.4 Importantly, acquired coagulopathy in these patients
worsens the prognosis. Therefore, early, aggressive, and rapid
hemostatic intervention are essential to prevent exsanguination and
avoid or minimize massive transfusion requirements.
Hemorrhage in trauma generally is the combined result of blood
loss and dilutional and consumption coagulopathy, with potentiat-
ing effects of acidosis, hypothermia, and electrolyte disturbance.
Moreover, severe tissue injury and hypoperfusion have been
identified as important drivers of an “endogenous” trauma-related
coagulopathy that is associated with poor outcome.5 According to
standard coagulation testing, approximately one quarter to one third
of all trauma patients are coagulopathic on admission to the
emergency department.6-8 This early coagulopathy is correlated
with increased transfusion requirement, prolonged intensive care
unit (ICU) stay, and a 4-fold increase in mortality.6,9 Fast
identification of the underlying cause of the coagulation disorder
is mandatory and represents the basis of the so-called “theragnostic
approach”. Although standard coagulation tests are used widely to
identify trauma-induced coagulopathy (TIC), the value of these
tests has been challenged in recent years.10,11 Routine coagulation
tests were not developed to identify trauma-related bleeding, and
these tests are neither predictive for bleeding nor validated for use
in patients with major trauma.12
Interesting alternatives are point-of-care viscoelastic assays,
such as rotational thromboelastometry (ROTEMs, TEM Innova-
tions GmbH, Munich, Germany) or thrombelastography (TEGs,
Haemonetics Corp, Niles, IL, USA), which are used increasingly
to diagnose TIC.10,13-17 This review summarizes present diag-
nostic strategies after major trauma and highlights current treat-
ment options for patients with severe bleeding trauma.
COAGULATION MONITORING IN TRAUMA
Standard coagulation tests such as prothrombin time (PT),
activated partial thromboplastin time (aPTT), and plasma
Journal of Cardiothoracic and Vascular Anesthesia, Vol 27, No 4S (August), 2013: pp S35–S43
This strategy addresses important confounders of the coagu-
lation process such as hemodilution, hypothermia, and acido-
sis; DCR is based on a damage control surgical approach,
permissive hypotension, and improvement of hemostatic com-
petence. Many studies have shown benefit in mortality when
using high ratios of fresh frozen plasma (FFP) to red blood cells
(RBC) as early treatment. However, there is increased aware-
ness that coagulation factor concentrate could be beneficial in
the treatment of trauma-induced coagulopathy.
& 2013 Elsevier Inc. All rights reserved.
KEY WORDS: hemorrhage, bleeding, trauma, transfusion,
coagulopathy, coagulation tests, goal-directed therapy,
damage control resuscitation, permissive hypotension
fibrinogen concentration are used widely in trauma centers
worldwide to diagnose TIC. However, these tests were not
developed to assess coagulopathy in acute bleeding situations
such as trauma.15 PT and aPTT provide information only on the
very initiation of clot formation, when only 5% of the entire
thrombin is generated.23 These tests also are influenced by low
levels (<1 g/L) of fibrinogen, making them unhelpful for
distinguishing between lack of coagulation factors and substrate.24
Moreover, none of these tests offers information on clot quality
and stability, which have been identified as important determi-
nants of TIC.13 Finally, waiting for test results is time consuming,
making them unsuitable in emergency conditions.13,25,26
Viscoelastic tests (VETs) such as ROTEMs and TEGs
have gained increasing interest for assessing coagulopathy in
trauma. In contrast to standard coagulation tests, VETs are
performed at the patient’s bedside using whole blood (not
plasma) samples; thus, the contribution of platelets and
fibrinogen to the clot kinetics can be assessed.
These methods provide a timely assessment of not only the
initiation of coagulation but also of the clot formation process
and the maximal clot strength (Fig 1).10,11,27 Furthermore,
VETs are considered the gold standard for diagnosing prema-
ture dissolution of the clot, which has been identified as an
important contributor to mortality (Fig 2).17,28-33
From the *Department of Anaesthesiology and Intensive Care
Medicine, AUVA Trauma Centre, Salzburg, Austria; †Ludwig Boltz-
mann Institute for Experimental and Clinical Traumatology, AUVA
Research Centre, Vienna, Austria; and ‡Dipartimento Emergenza
Urgenza, UOC Anestesia e Rianimazione, Ospedale dell’Angelo di
Mestre, Venice, Italy.
Description of research support: Dr. Schöchl has received research
support from TEM Innovations GmbH, Munich, Germany.
Address reprint requests to Associate Professor Herbert Schöchl,
MD, Department of Anaesthesiology and Intensive Care Medicine,
AUVA Trauma Centre, Franz Rehrl Platz 5, 5020 Salzburg, Austria.
Phone: 00436662 6580 2577, FAX: 0043662 6580 2486, E-mail:
Herbert.schoechl@auva.at
© 2013 Elsevier Inc. All rights reserved.
1053-0770/2601-0001$36.00/0
http://dx.doi.org/10.1053/j.jvca.2013.05.015
S35
S36 SCHÖCHL, GRASSETTO, AND SCHLIMP

Fig 1. (A) Normal ROTEM tracing. EXTEM, extrinsically activated test; FIBTEM, fibrin polymerization test using extrinsic activation plus
cytochalasin D, which inhibits platelet function. (B) Severe trauma-induced coagulopathy. Note prolonged clotting time (CT) and clot formation
time (CFT) and low maximal clot firmness (MCF) in the EXTEM test and very low MCF in the FIBTEM test.

EXTEM 2012-08-30 19:09 2: FIBTEM 2012-08-30 19:12 2:

CT: 154s CFT: 362s α: 42 CT: *5403s CFT: -s α: -

A10: 26mm A20: 34mm MCF: 35mm A10: - mm A20: - mm - MCF:* - mm

APTEM 2012-08-30 19:10 2: Tranexamic acid 2012-08-30 19:09 2:

CT: 143s CFT: 303 s α: 46 CT: 149s CFT: 366s α: 41

A10: 28mm A20: 36mm MCF: 39mm A10: 26mm A20: 35mm MCF: 38mm

Fig 2. ROTEM depicts severe hyperfibrinolysis. Note the immediate breakdown of the clot in the extrinsic activated test (EXTEM). No clot is
formed in the fibrin polymerization test (FIBTEM). The clot remains stable when aprotinin or tranexamic acid is added into the test cup (APTEM,
extrinsically activated test plus aprotinin).
MANAGEMENT OF TRAUMA HEMORRHAGE
Different reagents allow the evaluation of different aspects of
coagulation, including the stability and amplitude of the fibrin-
based clot (thromboelastometric FIBTEMs test [TEM] or func-
tional fibrinogen test [TEG]).34 Without the need for centrifuga-
tion, the turnaround times are short and the results are rapidly
available, so the development of the clot can be visualized in real
time. In some European trauma centers, VETs have been used
with success to guide hemostatic therapy in trauma.16,18-20,35,36
DAMAGE CONTROL RESUSCITATION
The most important aim in treating exsanguinating trauma
patients is immediate surgical control of bleeding. Abdominal
and extraperitoneal packing, closure of an open pelvic girdle,
and vascular embolization are common measures to mechan-
ically stop bleeding. Tourniquets and local hemostatic dressings
are temporary therapeutic options especially used in war fields,
with the same purpose. In addition, recent treatment concepts
take into account well-described contributors to trauma-related
coagulopathy, including dilutional coagulopathy, blood pres-
sure–related bleeding, hypothermia, acidosis, and fibrinolysis.
The concept of damage control surgery has been extended to a
more comprehensive damage control resuscitation (DCR) strat-
egy that implies permissive hypotension and fast hemostatic
treatment (Table 1).
About 80% of packed red blood cell units are transfused
within the first 6 hours after trauma patient admission.37 There-
fore, rapid and early identification of patients at risk for massive
transfusion is mandatory in order to initiate DCR and reduce
mortality. Failure to identify these patients early and to apply
DCR concepts is associated with excess mortality.38 Hypotension
and pulse are specific but not sensitive parameters because some
patients—especially the young—may present a “cryptic shock”
state with normal values even after significant blood loss.39
Massive transfusion scores using anatomic findings in combi-
nation with rapidly available laboratory tests such as hemoglobin
and base deficit were developed for early recognition of patients at
risk (Fig 3).40-43 Results with VETs also have shown a good
correlation with transfusional needs.44-48 A retrospective single-
center study using ROTEMs revealed that results after a 10-
minute running time were highly predictive for patients prone to
massive transfusion.49 Similar findings were reported by Holcomb
et al by using RapidTEGs in the emergency department.10
FLUID THERAPY
In the presence of hemorrhagic shock, fluid infusion repre-
sents the main treatment to improve perfusion, but aggressive
replacement increases dilution coagulopathy and interstitial
edema and impairs microcirculation, worsening oxygenation.15
Prehospital administration of high volumes (>3 L) of
crystalloid or colloid fluids was associated independently with
Table 1. Principles of Damage Control Resuscitation
● Minimize prehospital fluid therapy to avoid dilution coagulopathy.
● Allow permissive hypotension to avoid disruption of newly formed
clots.
● Aggressively manage temperature to avoid or treat hypothermia.
● Employ early and aggressive hemostatic therapy to avoid or treat
trauma-induced coagulopathy.
S37
100%
80%
60%
Sensitivity
40%
ABC Score
Lars on Score
20% Rainer Score
Schreiber Score
TASH Score
Vandromme Score
0%
0% 20% 40% 60% 80% 100%
100 - Specificity
Fig 3. Validation of 6 scoring systems and algorithms on 1
dataset (n ¼ 5,147) of severely injured patients extracted from the
TraumaRegister DGUs database. The TASH-Score and PWH/Rainer
showed superior performance over the others. (From Brockamp
et al43.)
a worse coagulation profile at emergency department admis-
sion.50 Data from the German trauma registry showed that
patients who received high-volume prehospital fluid therapy had
a significantly worse coagulation status, required more blood
products, and had higher incidence of organ failure compared
with matched patients receiving lesser amounts of fluid.51
Infusion of large quantities of crystalloids results in a non-
specific dilution of coagulation factors, coagulation inhibitors, and
platelets. In addition, artificial colloids exert specific alterations of
coagulation factors such as von Willebrand factor and factor VIII.
Thus, artificial colloids affect primary and secondary hemostasis.52
Furthermore, in vitro studies using VETs revealed that clot
strength decreased after dilution with artificial colloids.53 A meta-
analysis discovered a 4% higher mortality in trauma patients
receiving colloids compared with crystalloids.54 In part, this
finding could be linked to negative effects of colloids on blood
coagulation and platelet function.55 A recent randomized, double-
blind controlled study published by James et al56 compared
normal saline with 6% hydroxyethyl starch 130/0.4 (HES) in
patients sustaining either penetrating or blunt trauma. Among
patients with blunt trauma, the HES group received significantly
more blood products compared with those who received normal
saline only. There is actually no evidence on the superiority of
colloids over crystalloids in fluid resuscitation of trauma patients.57
DELIBERATE PERMISSIVE HYPOTENSION
Permissive hypotension is a strategy used to minimize or
withhold fluid therapy or vasopressor support until bleeding is
controlled either by surgical, radiologic, or pharmacologic
interventions.
Untreated hypovolemic shock provokes tissue hypoperfu-
sion and hypoxia.58 In contrast, aggressive fluid resuscitation
potentially increases blood pressure, thereby increasing
S38
hydrostatic forces on newly developed clots that could be
displaced. Thus, the goal is balance and not hypotension itself.
Animal studies of uncontrolled bleeding suggested improved
survival when blood pressure was not normalized but was
maintained low. Sondeen et al59 investigated rebleeding in a
porcine model. A standardized lesion of the infrarenal aorta
resulted in severe bleeding that stopped spontaneously when blood
pressure dropped. After cessation of bleeding, volume resuscitation
was initiated by lactated Ringer’s solution. The average systolic
pressure when rebleeding occurred was 94 ⫾3 mmHg.
Both limited-volume resuscitation and delayed resuscitation
by limited fluid replacement therapy have been implemented in
clinical practice.60 Recent European trauma guidelines recom-
mend a systolic blood pressure not higher than 80 to
100 mmHg in bleeding trauma patients without brain injury.61
This concept focuses on 2 goals: limiting crystalloid and/or colloid
fluid administration in order to reduce or minimize dilutional
coagulopathy, and accepting low systolic blood pressure until the
source of bleeding is under control. Although this concept is well
established clinically, scientific data are poor. Bickell et al62
reported improved survival in patients sustaining penetrating
truncal trauma when fluid therapy was delayed. However, patients
who died during transport were excluded from the analyses,
making the interpretation of these results difficult. Dutton et al63
investigated 2 different blood pressure targets during operative
care of bleeding trauma patients. Time to bleeding control was
shorter in the low-pressure group, with a target systolic blood
pressure of 70 mmHg, compared with the “higher” blood pressure
group, with a target of 100 mmHg. No difference in survival
was observed. Recently, Morrison et al64 investigated the effect
of a mean blood pressure of 50 mmHg versus a mean arterial
pressure of 65 mmHg. The lower blood pressure group received
fewer intraoperative fluids and fewer blood products, was less
likely to develop postoperative coagulopathy, and showed sig-
nificantly lower early mortality than the group with higher blood
pressure.
Brain trauma has been suggested as a contraindication of
this concept; however, prospective outcome data for patients
with a combination of uncontrolled bleeding and severe brain
trauma still are lacking.
RESTORATION OF BASELINE CONDITIONS
It is well known that anemia, acidosis, hypocalcemia, and
hypothermia are relevant in worsening coagulopathy. Thus,
restoring baseline conditions constitutes the first step in treating
the hemorrhagic trauma patient.
Red blood cells (RBCs) are fundamental not only to ensuring
adequate tissue oxygenation but also for hemostasis. Hematocrit
influences margination of platelets to endothelium and their
activation through adenosine diphosphate (ADP) release by
erythrocytes.65 Maintaining a hemoglobin level between 7 and 9
g/dL is recommended by recent European guidelines.61
Severe acidosis, mostly a result of shock-related tissue
hypoperfusion, impairs clotting factor activity, thrombin gen-
eration, and platelet adhesion and aggregation and enhances
fibrinogen degradation.66 Platelet counts and fibrinogen levels
have been shown to be reduced in acidotic animals.67 Different
studies have shown that reversal of acidosis alone did not
SCHÖCHL, GRASSETTO, AND SCHLIMP
correct coagulopathy; it may be speculated that the contempo-
raneous supplementation of clotting factors is needed.
Hypocalcemia has been shown to be correlated with poor
prognosis in trauma patients.68 Calcium is fundamental to
hemostasis through its bridge effect with negatively charged
surfaces of vitamin K–dependent factors and phospholipids.66
It also acts on platelets’ activity and on their morphologic
change. Hemodilution and infusion of blood products contain-
ing citrates often are responsible for hypocalcemia in trauma
patients. Calcium should be maintained above 0.9 mmol/L.61,66
Hypothermia is common in trauma patients and is associated
with the development of coagulopathy, multiorgan failure, and
increased mortality.69,70 Reynolds et al71 reported recently that 34%
of major trauma patients who received massive transfusion had a
nadir temperature lower than 341C. Hypothermia affects both
platelet function and plasmatic coagulation factors.72,73 Moreover,
hypothermia may increase fibrinolytic breakdown of the clot.74
The key risk factor for the onset of hypothermia is the severity
of tissue trauma and shock; however, environmental conditions
and prehospital medical care also are important confounders.75
A prospective randomized study revealed that a hypothermia
correction protocol reduced resuscitation requirements and dimin-
ished mortality.76 In summary, the prevention and early treatment
of acidosis, anemia, hypocalcemia, and hypothermia are part of
most massive transfusion algorithms.18-22
Early Hemostatic Intervention
Early enhancement of the hemostatic capacity has been
shown to improve outcome in patients with major trauma.35,77
In most trauma centers worldwide, coagulation therapy is based
on fresh frozen plasma (FFP), platelet concentrate (PC), and, in
some countries, cryoprecipitate.78-83 However, implementation
of massive transfusion protocols that favor an FFP-to-RBC
ratio of 1:1 has shown conflicting results. Some of these studies
reported a survival benefit using an FFP-to-RBC ratio close to
1:1,84-92 whereas other studies found no further improvement in
outcome when the ratio was higher than 1:2.37,93 A recent meta-
analysis of FFP-to-RBC ratios could not identify an additional
survival benefit of 1:1 over 1:2 ratios,94 and many such studies are
affected by a survivor bias.95
If RBCs, FFPs, and platelet concentrates are transfused in a
1:1:1 ratio in order to create “whole blood,” the remaining
solution contains an approximate hematocrit of less than 30%,
a platelet count of 80,000/mL, and a coagulation factor of 60%;
therefore, dilution is inevitable.96 Thus, to sufficiently increase
hemostatic capacity in trauma patients, high-volume FFP
transfusion is needed.97 Moreover, data from the German
trauma registry revealed that only patients with a trauma-
associated severe hemorrhage (TASH) score >15, which is
associated with a high risk for massive transfusion, benefited
from a high FFP-to-RBC ratio.98 It is quite reasonable to expect
that patients with more severe bleeding may benefit from
higher ratios. In contrast, plasma administration in patients who
have not received massive transfusions is associated with an
increase in complications, especially acute respiratory distress
syndrome (ARDS), with no improvement in survival rates.99
Rather, time to hemostatic intervention seems to be a key
determinant of outcome in trauma patients.77,100 Transfusion of
MANAGEMENT OF TRAUMA HEMORRHAGE
FFP clearly is time consuming, because delivery from the blood
service and thawing are required and a high-volume load is
necessary to sufficiently increase the concentration of coagu-
lation factors.97 For example, Snyder et al100 reported that the
first FFP was given to patients in the emergency department at a
median of 93 minutes after arrival. A recent prospective,
observational, multicenter study by Holcomb et al101 has
addressed the effect on mortality of treatment with administra-
tion of varying FFP (or platelet)–to–RBC ratios. A high ratio
given within 6 hours improved in-hospital mortality, and the
benefit of a higher ratio diminished over time. This further
strengthens the principle of early hemostatic intervention.
However, when also considering morbidity, there are well-
known risks associated with FFP transfusion, such as
transfusion-related acute lung injury, transfusion-associated
circulatory overload, ARDS, transfusion-related immunomodu-
lation, and pathogen transmission.102-105 An alternative to
sufficiently increase hemostatic capacity of trauma patients with
severe bleeding is the use of coagulation factor concentrates.
GOAL-DIRECTED COAGULATION THERAPY BASED
ON COAGULATION FACTOR CONCENTRATES
Coagulation factor concentrates, such as fibrinogen concentrate,
cryoprecipitate, prothrombin complex concentrate, and recombi-
nant activated factor VII (rFVIIa), have been used in severely
injured trauma patients.78,106,107 The rationale for improving
fibrinogen concentration is the fact that fibrinogen seems to be
the most vulnerable coagulation factor in bleeding patients, reach-
ing critical levels earlier than any other coagulation protein.106-109
Rourke et al106 recently reported that low fibrinogen levels
were a common finding in patients with major trauma upon
admission to the emergency room and were associated strongly
with high injury severity scale (ISS) scores, high baseline
deficits, and low systolic blood pressure. Furthermore, FFP
alone was not sufficient to maintain fibrinogen concentration
even though FFP and RBCs were transfused in a 1:2 ratio.
Only supplementation of cryoprecipitate resulted in mainte-
nance of an adequate fibrinogen content.
Chambers et al108 found that fibrinogen deficiency was
almost always the initial hemostatic abnormality in patients
with severe trauma and that a change in hemostatic therapy
toward a high ratio of FFP to RBCs was not sufficient to
overcome fibrinogen depletion within the first 4 hours of
treatment. Thus, FFP is not a suitable hemostatic therapy to
restore fibrinogen levels to those necessary for normal clot
formation. Current European guidelines suggest a target of 1.5
to 2 g/L or supplementation according to results of VETs.61
The amount of fibrinogen administered to trauma patients has
been reported to correlate with survival.110 Reduced need of
transfusion of allogeneic products also has been shown by studies
in different settings.36,111,112 Human fibrinogen concentrate (FC)
and cryoprecipitate provide a source for increasing plasma
fibrinogen concentration.83 Cryoprecipitate has disappeared from
the market in most European countries because of safety concerns,
in particular the risk of pathogen transmission.113 Moreover, the
fibrinogen content of a unit of cryoprecipitate is uncertain and a
wide range of fibrinogen concentration in each unit has been
reported (range, 120-796 mg).114 Recent European guidelines for
S39
massive trauma-related bleeding suggested a dose of 3 to 4 g of
fibrinogen concentrate or 50 mg/kg of cryoprecipitate, which is
approximately equivalent to 15 to 20 units in a 70-kg adult.61
Schöchl et al107 showed that despite a high cumulative
median dose of FC over a 24-hour period, the median post-
operative plasma fibrinogen level was below the reference range
of laboratory values; this finding suggests that treatment with FC
is unlikely to provoke postoperative hypercoagulability. Poten-
tially, FC also may correct or compensate for other hemostatic
defects associated with hemodilution, such as decreases in
platelet count or reduced quality of fibrin polymerization.115,116
Thrombin is paramount for the structure and the quality of the
clot—whereas low levels give birth to porous clots composed of
thick fibrin fibers, high concentrations produce a dense network of
thin fibers, resulting in a clot more resistant to mechanical and
fibrinolytic forces.117 To improve thrombin generation, prothrombin
complex concentrates (PCCs) are used in many European trauma
centers.18,35,107,118-120 In patients treated with vitamin K antagonists,
PCC administration resulted in fast normalization of the INR and
represents the gold standard for this process.121
Sound safety data still are lacking on the use of PCC in
bleeding trauma patients except in vitamin K antagonist
therapy. Josef et al122 reported an incidence of thromboembolic
events in the range of 6% after PCC administration in trauma
patients. Furthermore, limited information is available on the
combined use of FC and PCC in trauma patients. Favorable
outcomes have been reported after ROTEM-guided hemostatic
therapy with FC and PCC in major trauma; observed mortality
was lower than that predicted by the Revised Injury Severity
Classification score (RISC) and the Trauma Injury Severity
Score (TRISS).35 This treatment strategy eliminated delays
associated with standard coagulation testing and preparation of
allogeneic blood products for transfusion (eg, delivery from the
blood service and thawing); more than half the patients
received hemostatic therapy within an hour of admission to
the emergency department. By enabling early and aggressive
correction of coagulopathy and reduced transfusion of alloge-
neic blood products, ROTEM-guided, goal-directed use of
coagulation factor concentrates may contribute to reduced
mortality. Moreover, Innerhofer et al118 reported that trauma
patients who sustained comparable injuries showed better 24-
hour oxygenation variables and a lower incidence of multi-
organ failure and sepsis when treated with coagulation factors
only, compared with patients who received additional FFP.
According to recent evidence, tranexamic acid (TXA) should
be an integral part of massive transfusion protocols. The
CRASH-2 study revealed that trauma patients who were treated
with TXA within 3 hours after injury showed a 1.5% improved
survival rate.123,124 A study including combat causalities
reported a 13.7% improvement in survival in patients receiving
TXA and massive transfusion compared to a no-TXA group.125
CONCLUSIONS
Severe trauma still results in substantial morbidity and
mortality. Exsanguination potentially could be avoided by early
and aggressive coagulation therapy. VETs provide an important
insight in TIC and have the potential to guide hemostatic therapy
in a goal-directed way. Early and high FFP-to-RBC ratio
S40
therapy has been found to improve outcome. Coagulation
factor concentrates represent an alternative to avoid delays
and to increase hemostatic capacity. Immediate availability of
coagulation factor concentrates and sufficient increase of
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